Making Sense of Intention‐to‐Treat
Open accessAbstract
When analyzing data from randomized clinical trials, an intention-to-treat (ITT) analysis gives the highest level of evidence.However, this type of analysis is frequently the subject of both confusion and controversy.This article will review the ITT principle, why it is important, how it is applied and misapplied, and alternative strategies and their limitations. CASE STUDYThe Spine Patient Outcomes Research Trial (SPORT) on disk herniation will be used as a case study throughout this article [1].In this trial, 501 patients with disk herniation were randomized to receive surgery (lumbar diskectomy) or standard nonoperative care.The ITT analysis showed no effect for surgery, but both a non-ITT reanalysis of the data and a parallel observational cohort study [2] showed a strong benefit for surgery.These conflicting results incited much discussion and debate about the ITT approach (see Sidebar for more details). WHAT IS ITT?The ITT principle stipulates that all participants who are randomized must be included in the statistical analysis and analyzed according to the treatment group to which they were randomly assigned, regardless of what treatment, if any, they actually received.Thus, patients will be analyzed as a member of their initial randomization group even if they refuse or discontinue the intervention, "cross over" to another randomization group, miss follow-up measurements, or otherwise violate study protocol.In SPORT, only 60% of 245 patients randomized to surgery actually received surgery, but the ITT analysis counted all 245 as members of the surgery group.Similarly, 45% of 256 patients randomized to nonoperative care decided to undergo surgery sometime during the study, but the ITT analysis retained all 256 as members of the nonoperative care group. WHY ITT?The ITT analysis may seem, on first reflection, to run counter to common sense.If the patients didn't receive surgery, it seems unfair to count them as if they did.However, ITT has 2 strong rationales.First, it is necessary to preserve the strengths of randomization.The purpose of randomization is to ensure that potential prognostic factors are balanced between the treatment groups.This balance may be lost if some patients are excluded from the analysis or analyzed according to how they self-selected rather than how they were randomized.For example, excluding nonadherent patients may introduce bias because patients who adhere to treatments tend to have better outcomes regardless of whether the treatment is effective.In one study [3], those who adhered to the trial drug (clofibrate) had reduced mortality; but those who adhered to the placebo pill had the same reduction in mortality.Analyzing patients according to the treatment they actually received is also likely to bias the results; for example, if patients who self-select to surgery have a stronger belief in the efficacy of surgery this may create a spurious association between surgery and positive outcomes.It may seem justifiable to exclude patients who are nonadherent for reasons outside of their control, such as those who die before receiving treatment; but this can also create bias.Take a hypothetical example presented by Montori and Guyatt [4].In a stroke trial, patients are randomized to receive surgery or nonoperative care.Some patients in both study arms die early in the trial; because there is a lag between randomization and surgery, some patients in
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
A modified type of intention-to-treat analysis that excludes randomized patients who never started an intervention is frequently applied in the literature.
“Such a modified type of intention-to-treat analysis is frequently applied in the literature [27–29].”
From Is sleep disturbance in patients with chronic pain affected by physical exercise or ACT-based stress management? - A randomized controlled study (2018) · cites this paper as [29]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
What is meant by intention to treat analysis? Survey of published randomised controlled trials
Hollis, S., & Campbell, F. (1999) · BMJ · doi:10.1136/bmj.319.7211.670 · Cited by 2,160 · see citing works
Surgical vs Nonoperative Treatment for Lumbar Disk Herniation
Weinstein, J. N., Tosteson, T. D., Lurie, J. D., Tosteson, A. N. A., Hanscom, B. S., Skinner, J., Abdu, W. A., Hilibrand, A. S., Boden, S. D., & Deyo, R. A. (2006) · JAMA · doi:10.1001/jama.296.20.2441 · Cited by 1,108 · see citing works
Prentice, R. L., Caan, B., Chlebowski, R. T., Patterson, R., Kuller, L. H., Ockene, J. K., Margolis, K. L., Limacher, M. C., Manson, J. E., Parker, L. M., et al. (2006) · JAMA · doi:10.1001/jama.295.6.629 · Cited by 828 · see citing works
Surgical vs Nonoperative Treatment for Lumbar Disk Herniation
Weinstein, J. N., Lurie, J. D., Tosteson, T. D., Skinner, J., Hanscom, B. S., Tosteson, A. N. A., Herkowitz, H. N., Fischgrund, J. S., Cammisa, F. P., Albert, T. J., et al. (2006) · JAMA · doi:10.1001/jama.296.20.2451 · Cited by 764 · see citing works
Post-randomisation exclusions: the intention to treat principle and excluding patients from analysis
Fergusson, D., Aaron, S. D., Guyatt, G., & Hébert, P. (2002) · BMJ · doi:10.1136/bmj.325.7365.652 · Cited by 708 · see citing works
The Coronary Drug Project Research Group (1980) · New England Journal of Medicine · doi:10.1056/nejm198010303031804 · Cited by 659 · see citing works
The Intention-to-Treat Principle: How to Assess the True Effect of Choosing a Medical Treatment
Detry, M. A., & Lewis, R. J. (2014) · JAMA · doi:10.1001/jama.2014.7523 · Cited by 634 · see citing works
(2001) · Europe PMC (PubMed Central) · Cited by 442 · see citing works
Carlson, L. A., & Rössner, S. (1978) · Atherosclerosis · doi:10.1016/0021-9150(78)90051-5 · Cited by 315 · see citing works
Gravel, J., Opatrny, L., & Shapiro, S. (2007) · Clinical Trials · doi:10.1177/1740774507081223 · Cited by 135 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Weinstein JN, Lurie JD, Tosteson TD, et al. Surgery vs non-operative treatment for lumbar disk herniation: the Spine Patient Outcomes Research Trial (SPORT) Observational Cohort. JAMA 2006;296:2451-2459.
Cited by
Sorted by citations
Intention-to-treat concept: A review
Gupta, S. (2011) · Perspectives in Clinical Research · doi:10.4103/2229-3485.83221 · Cited by 1,921 · see citing works
A tutorial on sensitivity analyses in clinical trials: the what, why, when and how
Thabane, L., Mbuagbaw, L., Zhang, S., Samaan, Z., Marcucci, M., Ye, C., Thabane, M., Giangregorio, L., Dennis, B., Kosa, D., et al. (2013) · BMC Medical Research Methodology · doi:10.1186/1471-2288-13-92 · Cited by 893 · see citing works
Understanding the Intention-to-treat Principle in Randomized Controlled Trials
McCoy, E. (2017) · Western Journal of Emergency Medicine · doi:10.5811/westjem.2017.8.35985 · Cited by 767 · see citing works
Zhu, L.-Y., Chan, R., Kwok, T., Cheng, K. C.-C., Ha, A., & Woo, J. (2019) · Age and Ageing · doi:10.1093/ageing/afy179 · Cited by 179 · see citing works
Intention-to-treat versus as-treated versus per-protocol approaches to analysis
Ahn, E. J., & Kang, H. (2023) · Korean Journal of Anesthesiology · doi:10.4097/kja.23278 · Cited by 78 · see citing works
Barrett, K., & Stewart, I. (2021) · Health & Social Care in the Community · doi:10.1111/hsc.13074 · Cited by 73 · see citing works
Tek, C., Palmese, L. B., Krystal, A. D., Srihari, V. H., DeGeorge, P. C., Reutenauer, E. L., & Guloksuz, S. (2014) · Schizophrenia Research · doi:10.1016/j.schres.2014.10.002 · Cited by 59 · see citing works
“Data were analyzed according to modified intention-to-treat (ITT) principle, which included all randomized patients who received at least one dose of studymedication and had at least one post-baseline measurement (Sainani, 2010).”
MethodKimani-Murage, E. W., Griffiths, P. L., Wekesah, F. M., Wanjohi, M., Muhia, N., Muriuki, P. G., Egondi, T., Kyobutungi, C. K., Ezeh, A., McGarvey, S. T., et al. (2017) · Globalization and Health · doi:10.1186/s12992-017-0314-9 · Cited by 60 · see citing works
Kimani-Murage, E. W., Kyobutungi, C. K., Ezeh, A., Wekesah, F. M., Wanjohi, M., Muriuki, P., Musoke, R. N., Norris, S. A., Griffiths, P. L., & Madise, N. (2013) · Trials · doi:10.1186/1745-6215-14-445 · Cited by 54 · see citing works
Efficacy and safety of a soft contact lens to control myopia progression
valle, A. M. G., Blázquez, V., Gros-Otero, J., Cossío, M. I., Culebras, A., Verdejo‐García, A., Sebastián, J., García, M., Bueno, S., & Pinero, D. P. (2020) · Clinical and Experimental Optometry · doi:10.1111/cxo.13077 · Cited by 46 · see citing works
Wiklund, T., Linton, S. J., Alföldi, P., & Gerdle, B. (2018) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-018-2020-z · Cited by 45 · see citing works
Sezgin, D., & Esin, M. (2018) · Intensive and Critical Care Nursing · doi:10.1016/j.iccn.2018.02.007 · Cited by 45 · see citing works
Vincent, K. R., & Vincent, H. K. (2020) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000001450 · Cited by 39 · see citing works
Barbosa, M., Prada-López, I., Álvarez-Fernández, M., do Amaral, B., de Cal, M. C., & Tomás, I. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124249 · Cited by 36 · see citing works
Klein, A. A., & Seppala, M. D. (2019) · Journal of Substance Abuse Treatment · doi:10.1016/j.jsat.2019.06.009 · Cited by 35 · see citing works
Comino‐Suárez, N., Moreno, J. C., Megía‐García, Á., del‐Ama, A. J., Serrano‐Muñoz, D., Avendaño‐Coy, J., Gil-Agudo, A. M., Alcobendas-Maestro, M., López, E., & Gómez‐Soriano, J. (2025) · Journal of NeuroEngineering and Rehabilitation · doi:10.1186/s12984-025-01545-8 · Cited by 37 · see citing works
Methodological Challenges in Physical Activity Research With Older Adults
Chase, J. D. (2011) · Western Journal of Nursing Research · doi:10.1177/0193945911416829 · Cited by 34 · see citing works
Collins, J. E., Shrestha, S., Losina, E., Marx, R. G., Guermazi, A., Jarraya, M., Jones, M. H., Levy, B. A., Mandl, L. A., Williams, E. E., et al. (2022) · Arthritis & Rheumatology · doi:10.1002/art.42105 · Cited by 31 · see citing works
Zidén, L., Häggblom‐Kronlöf, G., Gustafsson, S., Lundin-Olsson, L., & Dahlin‐Ivanoff, S. (2013) · The Gerontologist · doi:10.1093/geront/gnt078 · Cited by 29 · see citing works
Heydarikhayat, N., Ashktorab, T., Rohani, C., & Zayeri, F. (2018) · Europe PMC (PubMed Central) · Cited by 28 · see citing works
Nonnato, A., Hulton, A. T., Brownlee, T. E., & Beato, M. (2020) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003591 · Cited by 28 · see citing works
Munn, J., & Small, J. (2017) · Evidence Based Library and Information Practice · doi:10.18438/b8qs9m · Cited by 27 · see citing works
Kimani-Murage, E. W., Kimiywe, J. O., Kabue, M., Wekesah, F. M., Matiri, E., Muhia, N., Wanjohi, M., Muriuki, P., Samburu, B. M., Kanyuira, J. N., et al. (2015) · Trials · doi:10.1186/s13063-015-0935-3 · Cited by 22 · see citing works
Cayzer, J., HEDDERLEY, D. I., & Gray, S. (2011) · Equine Veterinary Journal · doi:10.1111/j.2042-3306.2011.00455.x · Cited by 22 · see citing works
Sisson, S. B., Salvatore, A. L., Hildebrand, D. A., Poe, T., Merchant, C., Slawinski, M., Kracht, C. L., Stoner, J. A., Alcala, N. L., Schneider, L. A. F., et al. (2019) · Trials · doi:10.1186/s13063-019-3616-9 · Cited by 21 · see citing works
Efficacy of elaborated semantic features analysis in Aphasia: a quasi-randomised controlled trial
Efstratiadou, E.-A., Papathanasiou, I., Holland, R., Varlokosta, S., & Hilari, K. (2019) · Aphasiology · doi:10.1080/02687038.2019.1571558 · Cited by 20 · see citing works
Murdoch, E. M., Chapman, M. T., Crane, M. F., & Gucciardi, D. F. (2022) · Stress and Health · doi:10.1002/smi.3199 · Cited by 19 · see citing works
Lohmann-Jensen, R., Holsgaard‐Larsen, A., Emmeluth, C., Overgaard, S., & Jensen, C. (2014) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-15-110 · Cited by 18 · see citing works
Francis, T. R., & Abel, E. M. (2014) · Journal of Social Service Research · doi:10.1080/01488376.2013.875094 · Cited by 14 · see citing works
Koh, L. H., Hagger, M. S., Goh, V. H. H., Hart, W. G., & Gucciardi, D. F. (2017) · Journal of science and medicine in sport · doi:10.1016/j.jsams.2017.02.008 · Cited by 14 · see citing works
Rosenlund, S. V., Broeng, L., Jensen, C., Holsgaard‐Larsen, A., & Overgaard, S. (2014) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-15-354 · Cited by 13 · see citing works
Devereux, G., Winton, H. G. L., Black, J. M., & Beato, M. (2021) · Biology of Sport · doi:10.5114/biolsport.2021.102926 · Cited by 12 · see citing works
Baseman, J. G., Debra Revere, A., Painter, I. S., Oberle, M. W., Duchin, J. S., Thiede, H., Nett, R. J., MacEachern, D., & Stergachis, A. S. (2015) · Disaster Medicine and Public Health Preparedness · doi:10.1017/dmp.2015.139 · Cited by 11 · see citing works
A brief overview of sensitivity analyses
Kunselman, A. R. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.04.031 · Cited by 10 · see citing works
Singaravelu, G., Harley, C. B., Raffaele, J. M., Sudhakaran, P., & Suram, A. (2021) · OBM Geriatrics · doi:10.21926/obm.geriatr.2102168 · Cited by 10 · see citing works
Follow‐up in Childhood Functional Constipation
Modin, L., Walsted, A., Rittig, C. S., Hansen, A. V., & Jakobsen, M. S. (2015) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000000974 · Cited by 9 · see citing works
Markkula, A., Pyhälä-Neuvonen, R., & Stolt, S. (2024) · Early Human Development · doi:10.1016/j.earlhumdev.2024.106057 · Cited by 8 · see citing works
Intention-to-Treat Analysis in Clinical Research
Armijo-Olivo, S. L., da Silva, J. B., de Castro‐Carletti, E. M., de Oliveira‐Souza, A. I. S., Pelai, E. B., Mohamad, N., Baghbaninaghadehi, F., Dennett, L., Steen, J. P., Kumbhare, D. A., et al. (2024) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000002444 · Cited by 8 · see citing works
White, D. K., Hinman, R. S., Liles, S. C., Bye, T. K., Voinier, D., Copson, J., Schmitt, L., Bodt, B., & Jakiela, J. T. (2025) · Journal of Orthopaedic and Sports Physical Therapy · doi:10.2519/jospt.2025.13132 · Cited by 8 · see citing works
Inoue, M., Amimoto, K., Chiba, Y., Sekine, D., Fukata, K., Fujino, Y., Takahashi, H., & Makita, S. (2021) · Physical Therapy · doi:10.1093/ptj/pzab114 · Cited by 7 · see citing works
Bianchi, M., Anderson, L., Brownlee, T. E., Bossi, L., & Beato, M. (2022) · Biology of Sport · doi:10.5114/biolsport.2023.119287 · Cited by 6 · see citing works
Jensen, C., Roos, E. M., Kjærsgaard‐Andersen, P., & Overgaard, S. (2013) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-14-21 · Cited by 7 · see citing works
Sainani, K. L., & Popat, R. A. (2011) · PM&R · doi:10.1016/j.pmrj.2011.04.001 · Cited by 5 · see citing works
Self-citationLópez-Núñez, C., Fernández‐Artamendi, S., Ruiz-Aranda, D., Resurrección, D. M., & Navas-Campaña, D. (2024) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2024.101361 · Cited by 3 · see citing works
Donohue, C., Carnaby, G., & Garand, K. L. (2023) · American Journal of Speech-Language Pathology · doi:10.1044/2022_ajslp-22-00180 · Cited by 3 · see citing works
Proof of Concept, Feasibility, and Efficacy Trials
Chandelia, S. (2022) · Critical Care Medicine · doi:10.1097/ccm.0000000000005581 · Cited by 3 · see citing works
Understanding Intention to Treat Analysis and Per Protocol Analysis
Roshan, V. (2018) · Journal of Tumor Medicine & Prevention · doi:10.19080/jtmp.2018.03.555608 · Cited by 2 · see citing works
Özeke, Ö., Çay, S., Özcan, F., Topaloğlu, S., & Aras, D. (2019) · European Journal of Arrhythmia & Electrophysiology · doi:10.17925/ejae.2019.5.1.17 · Cited by 2 · see citing works
Sainani, K. L. (2012) · American Journal of Public Health · doi:10.2105/ajph.2012.300697 · Cited by 2 · see citing works
Self-citationRomero, D., Moriano, J. A., & Sagarduy, J. L. Y. (2026) · Salud Mental · doi:10.17711/sm.0185-3325.2026.16 · Cited by 1 · see citing works
Tratamiento fisioterapéutico de la heminegligencia secundaria a un accidente cerebrovascular
Cid-Guede, E., González-González, Y., & Carrera, I. D. C. (2020) · Archivos de Neurociencias · doi:10.31157/an.v23i2.10 · Cited by 1 · see citing works
Perceived and measured health benefits of aqua-based exercise for older adults with osteoarthritis
Fisken, A. (2013) · Tuwhera (Auckland University of Technology)
Vitamins in Nitrous Oxide Randomized Trial: A Few Concerns
Saikia, P. (2014) · Anesthesiology · doi:10.1097/aln.0000000000000092
EVALUATING A BYSTANDER INTERVENTION PROGRAM ON REPRODUCTIVE COERCION
Starnes, C. P. (2016) · UKnowledge (University of Kentucky) · doi:10.13023/etd.2016.507
Family Dependency Drug Courts: An Empirical Test Of Therapeutic Jurisprudence
Lindsey-Mowery, E. (2013) · Journal of International Crisis and Risk Communication Research
Francis, T. R. (2011) · Journal of International Crisis and Risk Communication Research
Adib‐Hajbaghery, M., Nabizadeh‐Gharghozar, Z., & Nasirpour, P. (2019) · Journal of Family Medicine and Primary Care · doi:10.4103/jfmpc.jfmpc_186_19
Westas, M. (2022) · Linköping University Medical Dissertations · doi:10.3384/9789179293796
Is Rivaroxaban Superior to Enoxaparin for Thromboprophylaxis in Hospitalized Patients of COVID-19?
Deokar, K. K. (2022) · Journal of the Association of Physicians of India · doi:10.5005/japi-11001-0087
Impact of Primary-Site Local Therapy for Patients with De Novo Metastatic Breast Cancer
Makris, E. A., & Soran, A. (2022) · Annals of Surgical Oncology · doi:10.1245/s10434-022-12871-9
White, D. K., Jakiela, J. T., Liles, S. C., Master, H., Voinier, D., Brunette, M., Copson, J., Bye, T., Schmitt, L., & Thoma, L. M. (2025) · Physical Therapy · doi:10.1093/ptj/pzaf140
The effect of foot positioning on tissue oxygenation in diabetic foot ulcers
Khani, F., Kazemzadeh, G., & Arian, M. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113453
- Authors
- Sainani, K. L.
- Affiliations
- Stanford University (US)
- Corresponding author
- Sainani, Kristin L.
- ORCID
- Sainani, Kristin L.
- Venue
- PM&R
- Publisher
- Wiley
- Published
- 2010-03
- Volume
- 2
- Issue
- 3
- Pages
- 209-213
- ISSN
- 1934-1482 (ISSN-L)
- 1934-1563
- OpenAlex
- W2097918448
- Cited by
- 62
- References
- 10
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 7 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- PM&R (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Keywords
- intention-to-treat analysis, randomized controlled trials, Spine Patient Outcomes Research Trial, disc herniation, medication adherence, crossover, bias in treatment effect estimation, treatment effect estimation, statistical power, treatment effect heterogeneity, treatment effect generalizability
- MeSH terms
- Data Interpretation, Statistical, Humans, Intention to Treat Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
